Switchable Na+ and K+ selectivity in an amino acid functionalized 2D covalent organic framework membrane

Biological cell membranes can efficiently switch Na+/K+ selectivity in response to external stimuli, but achieving analogous functions in a single artificial membrane is challenging. Here, we report highly crystalline covalent organic framework (COF) membranes with well-defined nanochannels and coordinative sites (i. e., amino acid) that act as ion-selective switches to manipulate Na+ and K+ transport. The ion selectivity of the COF membrane is dynamic and can be switched between K+-selective and Na+-selective in a single membrane by applying a pH stimulus. The experimental results combined with molecular dynamics simulations reveal that the switchable Na+/K+ selectivity originates from the differentiated coordination interactions between ions and amino acids. Benefiting from the switchable Na+/K+ selectivity, we further demonstrate the membrane potential switches by varying electrolyte pH, miming the membrane polarity reversal during neural signal transduction in vivo, suggesting the great potential of these membranes for in vitro biomimetic applications.

resulting COF-Cys-80% membrane was washed with deionized water (5 × 50 mL) to remove the residual L-cysteine and initiator. Finally, the COF-Cys-80% membrane was dried at 50 o C under vacuum for 24h.

COF-V-60% powder
COF-V-60% powder was synthesized according to the reference with a minor modification 1 . Typically, 0.05 mM of TAPB, 0.045 mM of PDA-V and 0.03 mM of PDA-OMe was dissolved in 10 mL acetonitrile by sonication for 5 min, followed by adding 0.5 mL 12 M acetic acid solution. The reaction mixture was kept undisturbed at room temperature (20 o C ± 2 o C) for 72h. The precipitate was collected by centrifugation, washed three times with acetonitrile, THF and ethanol, respectively. Finally, the powder collected was dried at 50 o C under vacuum for 24h in a yield of ~90%.

COF-V-30% powder
0.05 mM of TAPB, 0.0225 mM of PDA-V and 0.0525 mM of PDA-OMe was dissolved in 10 mL acetonitrile by sonication for 5 min, followed by adding 0.5 mL 12 M acetic acid solution. The reaction mixture was kept undisturbed at room temperature (20 o C ± 2 o C) for 72h. The precipitate was collected by centrifugation, washed three times with acetonitrile, THF and ethanol, respectively. Finally, the powder collected was dried at 50 o C under vacuum for 24h in a yield of ~92%.

COF-V-80% powder
0.05 mM of TAPB, 0.06 mM of PDA-V and 0.015 mM of PDA-OMe was dissolved in 10 mL acetonitrile by sonication for 5 min, followed by adding 0.5 mL 12 M acetic acid solution. The reaction mixture was kept undisturbed at room temperature (20 o C ± 2 o C) for 72h. The precipitate was collected by centrifugation, washed three times with acetonitrile, THF and ethanol, respectively. Finally, the powder collected was dried at 50 o C under vacuum for 24h in a yield of ~87%.

Fourier-transform infrared spectroscopy (FT-IR)
FT-IR spectra of monomers, COF membranes and L-cysteine were recorded on a Nicolet iS10 FT-IR spectrometer equipped with an attenuated total reflection (ATR) in the wavenumber range of 4000-500 cm -1 Solid-state 13 C cross-polarization nuclear magnetic resonance ( 13 C NMR) Free-standing COF membranes were obtained by removing the PAN support in DMF. The solid-state 13 C NMR spectra of the free-standing COF membranes were recorded on a Bruker 400M WB NMR spectrometer.

X-ray photoelectron spectroscopy (XPS)
The X-ray photoelectron spectroscopy (XPS) analyses were carried out on the Kratos Axis Ultra DLD spectrometer with a monochromatic Al Kα X-ray source (1486.6 eV).

Powder X-ray diffraction (PXRD)
PXRD pattern of COF-V-x% powder was collected on a Bruker D8 Twin diffractometer equipped with a Cu Kα radiation source (λ = 1.5406 Å) operating at 40-kV acceleration and 40 mA from 1.5 to 30 o with a step size of 0.02 o .

Grazing incidence wide-angle X-ray scattering (GIWAXS)
GIWAXS measurements were carried out on a Bruker D8 Discover system equipped with a multimode Eiger 2 R 500 K 2D detector. Membrane samples were cut into 1 × 1 cm 2 pieces and mounted onto a silicon zero background sample holder. The grazing incidence angle was set at 0.5 o . Then, GIWAXS data was collected at room temperature over the 2θ range of 1.5-16 o with an increment of 0.01 o and a 0.5 s /step.

Field-emission scanning electron microscopy (FE-SEM)
The surface morphology of COF membranes was observed by SEM on a Nova Nano 430 scanning electron microscope at the voltage of 5 kV and current of 56 pA, respectively. The membrane samples were coated with a 4-nm-thick iridium layer (Quorum Q150T sputter coater) before SEM imaging.

High resolution transmission electron microscope (HR-TEM)
Low-dose high resolution transmission electron microscope (HR-TEM) imaging were carried out on a Cscorrected FEI G2 cubed Titan 60-300 electron microscope equipped with a Gatan K2 Summit directdetection electron-counting camera operated under 300 kV. The COF active layer was first obtained by removing the PAN support in DMF and washed with DMF (5 × 30 mL) to remove the residual PAN polymer adsorbed on the COF active layer. Then the COF active layer was transferred onto a Cu grid for HR-TEM imaging.

Nitrogen sorption
The nitrogen sorption isotherms at 77 K were collected by using Micromeritics ASAP 2420 surface area and pore size analyzer. The free-standing COF active layer samples was first prepared by removing PAN support in DMF, and washed with DMF for 5 times to fully remove the PAN adsorbed on COF surface. ~50 mg of the COF active layer samples were degassed at 120 o C for 24h under vacuum and then subjected to N2 sorption measurement. Brunauer-Emmett-Teller (BET) surface areas were calculated from the linear region of the N2 isotherm in the P/P0 range from 0.04 to 0.2 and the pore size distribution was calculated by using the non-local density functional model (NLDFT) method.

Ion diffusion experiment
Ion diffusion test was performed using a homemade H-shaped diffusion cell. COF membrane samples were The diffusion coefficient of Na + and K + through COF membranes can be calculated from the following equation 2 : where J is the permeation rate. ΔC is the concentration gradient (0.1 M). D refers to the diffusion coefficient and d is the thickness of the whole membrane (the thickness of the PAN support and COF membrane are ~150 μm and ~50 nm, respectively). A is the testing membrane area (0.5 cm 2 ) and Aeff is the effective pore area (~0.05 cm -2 ).

Regulation of membrane potential
A piece of COF-Cys-60% membrane was mounted between two chambers of an electrochemical cell.
Chamber A was filled with 100mM of NaCl and 5 mM of KCl solutions, and chamber B was filled with 100mM of KCl and 5 mM of NaCl solutions. Two Ag/AgCl electrodes (5 mm × 20 mm × 0.2 mm) were used to measure the membrane potential. The membrane potential of COF-Cys-60% membrane was continuously recorded using a source meter (KEITHLEY, 2450 sourceMeter ® ). The pH values of the two solutions were switched between 3.8 and 8.9. After each pH adjustment, the membrane potential was recorded for 300 s.

Simulation details
All the MD simulations in this work were performed in the NVT ensemble by Gromacs 4.5.7 package 3 .
The periodic boundary condition was applied to all of the three directions. A time step of 1 fs was used. A temperature of 298 K was maintained using the Nosé-Hoover thermostat 4 . The OPLS all-atom force field was used to describe the COFs 5 . The heavy atoms in COFs remained fixed in all the simulations. The particle mesh Ewald (PME) summation was used to calculate the long-range electrostatic interaction 6 , with a cutoff of 1.3 nm for the separation of the direct and reciprocal space summation. The cutoff distance for the van der Waals interaction was 1.3 nm, and the parameters of the Lennard-Jones potential for the cross interactions between non-bonded atoms were obtained from the venerable Lorentz-Berthelot combination rule 7 .
In all MD simulations, the simulation systems consisted ~67600 atoms with dimensions of approximately 7.24 × 6.27 × 15.0 nm 3 , which were constructed by a graphene wall, a 5-layer COF membrane, ~ 20000 TIP3P water molecules 8 and ions ((i) K + /Cl -1000 mM; (ii) Na + /Cl -1000 mM, and (iii) K + /Cl -1000 mM and Na + /Cl -1000 mM). Here, a graphene was introduced into the simulation box to eliminate problems caused by finite boundaries, so that the COF membrane is the only pathway for ions transport between the left side and the right side of COF membrane. Then 60 ns simulation was performed for each system. The first 30 ns was discarded in each simulation trajectory for thermodynamic equilibration, followed by a 30 ns of production run.
The concentration of K + /Na + is 1 M NaCl/1 M KCl for MD simulation, which can be explained as follows: Firstly, a 5-layer COF membrane was used in the simulation, which contains 120 e charges (-COO -).
Therefore, there should be 120 Na + /K + to keep the system electrically neutral. Secondly, the time scale of MD simulation trajectories is typically on the order of tens of nanoseconds. Thus, additional K + /Na + should be available in the simulation box to study the transport behavior. That means the number of K + /Na + should be more than 120 in the simulation box. Considering the volume of the simulation box, the minimum concentration of K + /Na + should be 0.67 M. Therefore, the feed solution was 1 M Na + /1 M K + for the MD simulation.

Supplementary Figures
Supplementary Fig. 1 Cross-section SEM images of COF-V-60% membranes with various thickness.